摘要目的 探讨健康志愿者单次或多次局部外用不同浓度的他扎罗汀倍他米松乳膏后,健康皮肤对受试药物的耐受性,预测受试药物对人体皮肤潜在的不良反应及其强度.方法 34例单次给药受试者分为6组,分别进行他扎罗汀与倍他米松浓度均为0.025％、0.05％、0.1％、0.15％、0.2％、0.25％的单次给药耐受性试验.12例多次给药受试者分为2组,分别进行他扎罗汀与倍他米松浓度均为0.2％、0.15％每天给药1次、连续给药7d的多次给药耐受性试验.观察受试者给药前后体征、实验室检查、给药部位皮肤反应及主观感觉、内源性皮质醇水平的变化,以及经皮吸收进入系统循环的药物量.结果 试验中未发生严重不良事件.单次给药34例受试者用药后均未出现与受试药物有关的不良反应,各项观察指标均未发现与受试药物有关的异常改变.多次给药12例受试者在开始给药后0～7d给药部位无任何异常皮肤反应及自觉不适症状,给药后14 d(停药后7 d)0.2％组6例受试者中5例、0.15％组6例受试者中2例,给药部位皮肤出现轻度刺激反应症状;其他各项观察指标均未发现与受试药物有关的异常改变.结论 他扎罗汀与倍他米松乳膏单次给药的最大耐受剂量为0.25％他扎罗汀和0.25％倍他米松.0.15％他扎罗汀和0.15％倍他米松连续给药7d是比较安全的.

abstractsObjective To evaluate skin tolerance to creams containing different concentrations of tazarotene and betamethasone dipropionate in healthy volunteers after single or multiple applications,and to predict potential adverse effects of these creams as well as their degree.Methods Thirty-four healthy volunteers were enrolled in a single-dose trial group,and divided into six subgroups to receive single session of topical treatment with creams containing tazarotene and betamethasone dipropionate both at the concentrations of 0.025％,0.05％,0.1％,0.15％,0.2％ and 0.25％ respectively.Another 12 healthy volunteers were enrolled in a multiple-dose trial group,and divided into two subgroups to topically apply creams containing tazarotene and betamethasone dipropionate both at the concentrations of 0.2％ and 0.15％,respectively,once a day for 7 consecutive days.General status and subjective feelings of these testees were evaluated,skin reactions at application sites were observed,and routine laboratory examinations (including routine blood test,routine urine test,hepatic and renal function examination) were performed,before and after the application of these creams in both single-and multiple-dose trials.Endogenous cortisol levels were measured before and 7,14 days after the initial application of the creams,and the amount of drugs percutaneously absorbed into systemic circulation was determined before and 1,3,5,7 days after that in the multiple-dose trial.Results No serious adverse events were found in the study.In the single-dose trial,the testees showed no drug-related adverse reactions or abnormal changes in test patameters after the application of the creams.In the multiple-dose trial,no aberrant skin reaction or self-reported discomfort was noted in any of the testees from day 0 to 7 after the first initial application of the creams,but mild irritation occurred in 5 out of 6 volunteers applying the cream containing 0.2％ tazarotene and 0.2％ betamethasone dipropionate and in 2 out of 6 volunteers applying the cream containing 0.15％ tazarotene and 0.15％ betamethasone dipropionate on day 14,with no abnormal drug-related changes in the other test parameters.Conclusions The maximum tolerated concentration of both tazarotene and betamethasone dipropionate is 0.25％ when they are topically applied in a combined cream for one session.It is relatively safe to apply the cream containing 0.15％ tazarotene and 0.15％ betamethasone dipropionate for 7 consecutive days.